Our principal objective is to identify, isolate, characterize and study functions of molecules having primary importance in regulating animal cell cycle, and these functions' derangements in cancer. Significant evidence supports the view that animal cells reach a crucial control point during the G1 phase of the cycle from which they either continue to proliferate or detour to a quiescent state G0. Rapid protein synthesis seems critical in influencing this decision to grow or not to grow. In particular, we plan to localize the synthesis of regulatory protein (or proteins), both in time during G1 and within the cell. Using acrylamide gels we will seek a protein specifically sythesized in conjunction with the observed kinetics of passage of the cell population through the control event. Its manner of synthesis will be examined in several environments with differing growth situations, in mutant cells with altered cell cycle controls, in cells transformed by DNA or RNA viruses or chemicals, and in revertants of the transformed cells. We plan to purify this protein, characterize it chemically, and study its properties related to cell cycle events. Cells selectively permeabilized to allow protein entry (without serious disruption of macromolecular synthesis) will be investigated for DNA (S phase) initiation by the protein. Longer term objectives are to study physiological mechanisms which activate the "on/off switch" in determining this protein's synthesis and to investigate functions required for S phase initiation in vitro.